The genetic diversity within the 1.4 kb HLA-G 5' upstream regulatory region moderately impacts on cellular microenvironment responses.

Abstract

The HLA-G 5'URR extending 1.4 kb from the ATG presents a unique set of regulatory elements among HLA genes. Several variable sites have been described that coincide with or are close to these elements, thus HLA-G 5'URR polymorphism might influence the HLA-G expression level. We cloned the ten most frequent HLA-G 5'URR haplotypes to evaluate their activity on a luciferase reporter gene in HLA-G+ cell lines (JEG-3/choriocarcinoma and FON+/melanoma). We also investigated associations between the plasma HLA-G (sHLA-G) levels and the HLA-G 5'URR variability in 157 healthy individuals. Cell lines were transfected with pGL3-Basic vector constructions containing HLA-G 5'URR sequences. The G010101a (in JEG-3) and G010101b (in FON+) haplotypes exhibited higher promoter activity, whereas the G010101d (in JEG-3) and G010102a (in FON+) haplotypes exhibited lower promoter activity. In the presence of HLA-G inducers (interferon-β and progesterone) or repressors (cyclopamine) HLA-G promoter activity was modulated, but certain haplotypes exhibited differential responses. No strict association was observed between plasma sHLA-G levels and the 5'URR haplotypes or genotypes; however, the G010101b haplotype was underrepresented among HLA-G-negative plasmas. Therefore, the HLA-G 5'URR polymorphism may have an impact on the modulation of HLA-G gene expression, but alone provides a limited predictive value for sHLA-G levels in vivo.

• Authors: Fabrício C Dias, Bruna C Bertol, Isabelle Poras, Bruno M Souto, Celso T Mendes-Junior, Erick C Castelli, Laure Gineau, Audrey Sabbagh, Nathalie Rouas-Freiss, Edgardo D Carosella, Eduardo A Donadi, Philippe Moreau
• Journal: Scientific reports (Sci Rep) Vol. 8 Issue 1 Pg. 5652 (04 04 2018) ISSN: 2045-2322 [Electronic] England
• PMID: 29618829 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 5' Untranslated Regions
• HLA-G Antigens
• Transcription Factors

Topics

• 5' Untranslated Regions (genetics)
• Adult
• Cellular Microenvironment
• Choriocarcinoma (genetics, pathology)
• Female
• Genotype
• HLA-G Antigens (genetics, metabolism)
• Haplotypes
• Humans
• Male
• Melanoma (genetics, pathology)
• Polymorphism, Single Nucleotide
• Regulatory Sequences, Nucleic Acid
• Transcription Factors (metabolism)
• Tumor Cells, Cultured